Older grandfathers pass on autism risk through generations

Men who have children at older ages are more likely to have grandchildren with autism compared to younger grandfathers, according to new research. This is the first time that research has shown that risk factors for autism may accumulate over generations.

The study led by King's College London's Institute of Psychiatry, Karolinska Institutet in Sweden and the Queensland Brain Institute in Australia is published today in JAMA Psychiatry.

By using Swedish national registers, researchers identified 5,936 individuals with autism and 30,923 healthy controls born in Sweden since 1932. They had complete data on each individual's maternal and paternal grandfathers' age of reproduction and details of any psychiatric diagnosis.

The study found that the risk of autism in the grandchild increased the older the age of the grandfather at the time his son or daughter was born. Men who had a daughter when they were 50 or older were 1.79 times more likely to have a grandchild with autism. Men who had a son when they were 50 or older were 1.67 times more likely to have a grandchild with autism, compared to men who had children when they were 20-24.

Dr Avi Reichenberg, from King's Institute of Psychiatry and co-author of the paper says: "We tend to think in terms of the here and now when we talk about the effect of the environment on our genome. For the first time in psychiatry, we show that your father's and grandfather's lifestyle choices can affect you. This doesn't mean that you shouldn't have children if your father was old when he had you, because whilst the risk is increased, it is still small. However, the findings are important in understanding the complex way in which autism develops."

Emma Frans, lead author of the study from Karolinska Institutet says: "We know from previous studies that older paternal age is a risk factor for autism. This study goes beyond that and suggests that older grandpaternal age is also a risk factor for autism, suggesting that risk factors for autism can build up through generations."

In the UK, approximately 1 in 100 adults have an autism spectrum disorder (ASD), with the condition affecting more men than women. The condition affects people in very different ways: some are able to live relatively everyday lives, while others will require a lifetime of specialist support. People with ASD have difficulty communicating with and relating to other people, and making sense of the world around them.

Autism is known to be caused by a combination of genetic and environmental factors. Previous studies have shown that older paternal age is a risk factor for autism in children: fathers aged 50 or older have a more than doubled risk to have a child diagnosed with autism compared to younger fathers.

The mechanism behind this link is unknown, but may be explained by mutations occurring in the male sperm cells. Sperm cells divide over time, and on each division the genome is faced by the possibility of new mutations being introduced.

However, most genetic mutations do not result in the child developing autism. The new findings suggest that these 'silent' mutations are passed on to the otherwise healthy child, but may influence the risk of future generations developing autism. The authors suggest that genetic risk could accumulate over generations, or could interact with other risk factors, until it reaches a threshold resulting in the disorder manifesting itself.

Funding: The study was supported by the Swedish Research Council, the Swedish Council for Working Life and Social Research and the Karolinska Institutet.

About King's College London:

King's College London is one of the top 30 universities in the world (2012/13 QS international world rankings), and was The Sunday Times 'University of the Year 2010/11', and the fourth oldest in England. A research-led university based in the heart of London, King's has more than 24,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and more than 6,100 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £525 million (year ending 31 July 2011).

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.

The College is in the midst of a five-year, £500 million fundraising campaign - World questions|King's answers - created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign's three priority areas are neuroscience and mental health, leadership and society, and cancer. More information about the campaign is available at http://www.kcl.ac.uk/kingsanswers.

About Karolinska Institutet:

Karolinska Institutet is one of the world's leading medical universities. It accounts for over 40 per cent of the medical academic research conducted in Sweden and offers the country's broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine. Website: ki.se/English

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